GIP — glucose-dependent insulinotropic polypeptide, historically gastric inhibitory polypeptide — is a 42-amino-acid incretin secreted by K-cells in the duodenum and proximal jejunum in response to nutrients, particularly fat and glucose. Together with GLP-1 it accounts for the incretin effect, the observation that oral glucose provokes a larger insulin response than an intravenous load producing the same blood glucose.
Receptor and reported biology
The GIP receptor is a class B GPCR found on pancreatic beta-cells, adipocytes, bone and regions of the central nervous system. Published work describes glucose-dependent potentiation of insulin secretion, effects on adipose lipid handling and blood flow, and central effects on food intake. GIP's role in energy balance has been genuinely contested — both agonism and antagonism at the receptor have been reported to reduce body weight in rodent models, and the mechanism remains an open research question. Like GLP-1, native GIP is rapidly cleaved by DPP-4.
Why it matters
GIP is the second arm of dual incretin pharmacology. Tirzepatide is a GIP/GLP-1 dual agonist built on a GIP-based backbone, which is why GIP receptor biology moved from a footnote to a central topic in metabolic research.
Related terms
triple agonist · GLP-1 receptor agonist. See the GIP research family, Tirzepatide, and what tirzepatide is.